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  • CALB-Catalyzed Two-Step Alcoholytic Desymmetrization of 3-Methylglutaric Diazolides in MTBE.

CALB-Catalyzed Two-Step Alcoholytic Desymmetrization of 3-Methylglutaric Diazolides in MTBE.

Applied biochemistry and biotechnology (2017-12-16)
Ting-Yi Wu, Yuan-Rong Lai, Shau-Wei Tsai
ABSTRACT

Optically pure 3-substituted glutarates can be prepared from the alcoholic ring-opening of cyclic anhydride derivatives, esterification of 3-substituted glutaric acid, and hydrolysis, alcoholysis, aminolysis, and ammonolysis of the diester derivatives via hydrolases or organocatalysts. Unfortunately, most of them mainly focus on the first-step desymmetrization, leading to the difficulty on producing optically pure enantiomers. As a general trend in lipase-catalyzed desymmetrization of 3-methylglutarates, poorer enantiomeric excesses with lower chemical yields were found, as the methyl substituent is relatively small to induce a high enzyme stereodiscrimination. The two-step desymmetrization for CALB-catalyzed alcoholysis of 3-methylglutaric di-1,2,4-triazolide 1a in anhydrous MTBE is first developed to increase the enzyme activity in each reaction step. The enantioselectivity for the second-step kinetic resolution is furthermore improved by using 3-methylglutaric dipyrazolide 1b as the substrate. The kinetic and thermodynamic analysis is, moreover, addressed for shedding insights into the desymmetrization process.

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4-Methyl-1-pentanol, 97%
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Sigma-Aldrich
Hexarelin, ≥90% (HPLC)
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